Hypoxia Stimulates the Epithelial-to-Mesenchymal Transition in Lung Cancer Cells Through Accumulation of Nuclear beta-Catenin

摘要

Background/Aim: Recent studies implied a significant role of hypoxia-inducible factor-1 alpha (HIF1 alpha) in cell transformation. This study aimed to assess the effects of HIF1 alpha on the epithelial-to-mesenchymal transition (EMT) and tumorigenesis of lung adenocarcinoma cells. Materials and Methods: Invasion, migration and colony formation assays were used to evaluate cell transformation. Expression of EMT-related markers were analyzed by western blot, reverse-transcription polymerase chain reaction or zymography. A luciferase assay was carried out to access the transcriptional activity of beta-catenin. Results: Hypoxia enhanced migration, invasion and transformation of A549 lung adenocarcinoma cells. Hypoxic stimulation promoted the expression of EMT-related markers in lung cancer cells. The expression of HIF1 alpha was found to be involved in hypoxia-mediated modulation of expression of snail family transcriptional repressors 1(SNA11) and 2(SLUG). Hypoxia enhanced nuclear accumulation and transcriptional activity of beta-catenin. Conclusion: beta-Catenin promotes expression of EMT-related genes and eventually contributes to the metastatic process.